This project investigates whether supplementation with vitamin E or beta-carotene reduces incidence of lung and other cancers. Several hypotheses related to cancer prevention, etiology (including gene-environment interactions), and early detection are also being tested. Research indicates a role in cancer prevention for certain micronutrients, including vitamin E and beta-carotene, based on antioxidant and other antineoplastic properties. The ATBC Study is a randomized, double-blind, placebo-controlled, 2x2 factorial intervention trial of daily supplementation with beta-carotene (20 mg) and/or vitamin E (50 mg dl-alpha-tocopheryl acetate) for 5-8 years. The 29,133 participants are 50-69 year old male cigarette smokers in southwestern Finland. Serum, toenails, and questionnaire data were collected at baseline, and serum, whole blood, and RBCs during followup. All cancers are identified through the national registry, with central medical record and pathology reviews. Active intervention concluded in 1993, and continued followup of the cohort examines post-trial incidence trends. Intervention results showed reduced incidence in the vitamin E group for prostate (32%) and colorectal (16%) cancers. Beta-carotene demonstrated no cancer preventive effects and resulted in increased lung cancer incidence (16%) and overall mortality (8%). Organ-specific intervention and cancer etiologic analyses are focused on a wide range of hypotheses including effects of antioxidants, vitamin D, folate/homocysteine, alcohol, steroid hormones, physical activity, and serum micronutrient concentrations. The predictive value of serum prostate-specific antigen (PSA) and pepsinogens, and H. pylori and C. pneumoniae titers have also been shown. Cancer risk related to several genetic polymorphisms are being investigated including those for GSTs, NATs, CYPs, methylene tetrahydrofolate-reductase and methionine synthase, RAR/RXR, androgen and vitamin D receptors, and alcohol dehydrogenase.